PH12013502033B1 - Pyrimidine derivatives for the treatment of viral infections - Google Patents
Pyrimidine derivatives for the treatment of viral infections Download PDFInfo
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- PH12013502033B1 PH12013502033B1 PH12013502033A PH12013502033A PH12013502033B1 PH 12013502033 B1 PH12013502033 B1 PH 12013502033B1 PH 12013502033 A PH12013502033 A PH 12013502033A PH 12013502033 A PH12013502033 A PH 12013502033A PH 12013502033 B1 PH12013502033 B1 PH 12013502033B1
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- 230000009385 viral infection Effects 0.000 title abstract description 6
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- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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Families Citing this family (162)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ME03782B (me) | 2011-04-08 | 2021-04-20 | Janssen Sciences Ireland Unlimited Co | Derivati pirimidina za tretman virusnih infekcija |
LT2776439T (lt) | 2011-11-09 | 2018-10-10 | Janssen Sciences Ireland Uc | Purino dariniai, skirti virusinų infekcijų gydymui |
KR20190007106A (ko) | 2011-12-21 | 2019-01-21 | 노비라 테라퓨틱스, 인코포레이티드 | B형 간염의 항바이러스성 제제 |
WO2014009509A1 (en) | 2012-07-13 | 2014-01-16 | Janssen R&D Ireland | Macrocyclic purines for the treatment of viral infections |
NZ743463A (en) | 2012-08-28 | 2019-09-27 | Janssen Sciences Ireland Uc | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
ES2701098T7 (es) | 2012-10-05 | 2021-02-03 | Janssen Sciences Ireland Unlimited Co | Derivados de acilaminopirimidina para el tratamiento de infecciones víricas y otras enfermedades |
ES2670513T3 (es) | 2012-10-10 | 2018-05-30 | Janssen Sciences Ireland Uc | Derivados pirrolo[3,2-d]pirimidínicos para el tratamiento de infecciones víricas y otras enfermedades |
MX361585B (es) | 2012-11-16 | 2018-12-11 | Janssen Sciences Ireland Uc | Derivados 2-aminoquinazolínicos sustituidos heterocíclicos para el tratamiento de infecciones víricas. |
UA118751C2 (uk) * | 2013-02-21 | 2019-03-11 | ЯНССЕН САЙЄНСІЗ АЙРЛЕНД ЮСі | Похідні 2-амінопіримідину для лікування вірусних інфекцій |
DK2961732T3 (en) | 2013-02-28 | 2017-07-10 | Janssen Sciences Ireland Uc | SULFAMOYLARYLAMIDS AND USE THEREOF AS MEDICINES TO TREAT HEPATITIS B |
US8993771B2 (en) | 2013-03-12 | 2015-03-31 | Novira Therapeutics, Inc. | Hepatitis B antiviral agents |
EA202090547A3 (ru) | 2013-03-29 | 2020-12-30 | Янссен Сайенсиз Айрлэнд Юси | Макроциклические деаза-оксипурины для лечения вирусных инфекций |
WO2014161888A1 (en) | 2013-04-03 | 2014-10-09 | Janssen R&D Ireland | N-phenyl-carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
EP3004074B1 (en) | 2013-05-24 | 2017-10-25 | Janssen Sciences Ireland UC | Pyridone derivatives for the treatment of viral infections and further diseases |
DK3030563T3 (da) | 2013-06-27 | 2017-11-20 | Janssen Sciences Ireland Uc | Pyrrolo-[3,2-d]-pyrimidin-derivater til behandling af virale infektioner og andre sygdomme |
LT3024819T (lt) | 2013-07-25 | 2018-06-11 | Janssen Sciences Ireland Uc | Pirolamido dariniai, turintys glioksamido pakaitų, ir jų panaudojimas kaip vaistų hepatito b gydymui |
MX368625B (es) * | 2013-07-30 | 2019-10-08 | Janssen Sciences Ireland Uc | Derivados de tieno[3,2-d]pirimidinas para el tratamiento de infecciones virales. |
JP6452119B2 (ja) | 2013-10-23 | 2019-01-16 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | カルボキサミド誘導体およびb型肝炎の処置のための医薬品としてのその使用 |
US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9181288B2 (en) | 2014-01-16 | 2015-11-10 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
EP3102225B1 (en) | 2014-02-05 | 2020-03-25 | Novira Therapeutics Inc. | Combination therapy for treatment of hbv infections |
CN110483484A (zh) | 2014-02-06 | 2019-11-22 | 爱尔兰詹森科学公司 | 氨磺酰基吡咯酰胺衍生物及其作为药物用于治疗乙型肝炎的用途 |
US9400280B2 (en) | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
EP3172190A1 (en) | 2014-07-24 | 2017-05-31 | Bayer CropScience Aktiengesellschaft | Fungicidal pyrazole derivatives |
PL3321265T3 (pl) | 2015-03-04 | 2020-11-16 | Gilead Sciences, Inc. | Związki 4,6-diamino-pirydo[3,2-d]pirymidynowe i ich wykorzystanie jako modulatorów receptorów toll-podobnych |
WO2016149581A1 (en) | 2015-03-19 | 2016-09-22 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis b infections |
US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
JP2018525412A (ja) | 2015-08-26 | 2018-09-06 | ギリアード サイエンシーズ, インコーポレイテッド | 重水素化トール様受容体調節因子 |
CA2997955A1 (en) | 2015-09-15 | 2017-03-23 | Gilead Sciences, Inc. | Modulators of toll-like receptors for the treatment of hiv |
TW201718496A (zh) | 2015-09-29 | 2017-06-01 | 諾維拉治療公司 | B型肝炎抗病毒劑之晶型 |
KR20180087290A (ko) | 2015-11-27 | 2018-08-01 | 얀센 사이언시즈 아일랜드 유씨 | 인플루엔자 바이러스 감염에서 사용하기 위한 복소환식 인돌 |
EA202091898A1 (ru) | 2015-12-15 | 2021-06-22 | Джилид Сайэнс, Инк. | Антитела, нейтрализующие вирус иммунодефицита человека |
DK3405466T3 (da) * | 2016-01-20 | 2021-02-01 | Janssen Sciences Ireland Unlimited Co | Arylsubstituerede pyrimidiner til anvendelse ved influenzavirusinfektion |
AU2017248828A1 (en) | 2016-04-15 | 2018-11-01 | Janssen Sciences Ireland Uc | Combinations and methods comprising a capsid assembly inhibitor |
JP6770098B2 (ja) | 2016-05-27 | 2020-10-14 | ギリアード サイエンシーズ, インコーポレイテッド | Ns5a、ns5bまたはns3阻害剤を使用する、b型肝炎ウイルス感染症を処置するための方法 |
BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
US11053256B2 (en) | 2016-07-01 | 2021-07-06 | Janssen Sciences Ireland Unlimited Company | Dihydropyranopyrimidines for the treatment of viral infections |
JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
WO2018045150A1 (en) | 2016-09-02 | 2018-03-08 | Gilead Sciences, Inc. | 4,6-diamino-pyrido[3,2-d]pyrimidine derivaties as toll like receptor modulators |
SI3507276T1 (sl) | 2016-09-02 | 2022-01-31 | Gilead Sciences, Inc. | Spojine modulatorja toličnih receptorjev |
CA3037989A1 (en) * | 2016-09-29 | 2018-04-05 | Janssen Sciences Ireland Unlimited Company | Pyrimidine prodrugs for the treatment of viral infections and further diseases |
EP3526323B1 (en) | 2016-10-14 | 2023-03-29 | Precision Biosciences, Inc. | Engineered meganucleases specific for recognition sequences in the hepatitis b virus genome |
BR112019011284A2 (pt) * | 2016-12-05 | 2019-10-22 | Apros Therapeutics Inc | composto, composição farmacêutica, métodos de tratamento de uma condição, de hbv e de câncer, e, uso de um composto. |
AR110768A1 (es) | 2017-01-31 | 2019-05-02 | Gilead Sciences Inc | Formas cristalinas de tenofovir alafenamida |
JOP20180008A1 (ar) | 2017-02-02 | 2019-01-30 | Gilead Sciences Inc | مركبات لعلاج إصابة بعدوى فيروس الالتهاب الكبدي b |
CA3057813A1 (en) | 2017-03-29 | 2018-10-04 | Sumitomo Dainippon Pharma Co., Ltd. | Vaccine adjuvant formulation |
JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
TW202024061A (zh) | 2017-08-17 | 2020-07-01 | 美商基利科學股份有限公司 | Hiv蛋白質膜抑制劑之固體形式 |
AR112412A1 (es) | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas de sal de colina de un inhibidor de la cápside del vih |
AU2018319538B9 (en) | 2017-08-22 | 2021-05-27 | Gilead Sciences, Inc. | Therapeutic heterocyclic compounds |
EP3697755B1 (en) * | 2017-10-20 | 2021-09-15 | SABIC Global Technologies B.V. | Novel synthesis method for the preparation of dibenzoate compounds, such as 4-[benzoyl(methyl)amino]pentane-2-yl dibenzoate |
WO2019084060A1 (en) | 2017-10-24 | 2019-05-02 | Silverback Therapeutics, Inc. | CONJUGATES AND METHODS OF USE FOR THE SELECTIVE DELIVERY OF IMMUNOMODULATORY AGENTS |
US20210177827A1 (en) * | 2017-10-25 | 2021-06-17 | Children`S Medical Center Corporation | Papd5 inhibitors and methods of use thereof |
AU2018385693A1 (en) | 2017-12-15 | 2020-06-18 | Silverback Therapeutics, Inc. | Antibody construct-drug conjugate for the treatment of hepatitis |
CA3084582A1 (en) | 2017-12-20 | 2019-06-27 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
EP3728283B1 (en) | 2017-12-20 | 2023-11-22 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
WO2019124500A1 (ja) | 2017-12-21 | 2019-06-27 | 大日本住友製薬株式会社 | Tlr7アゴニストを含む併用薬 |
MX2020008404A (es) | 2018-02-13 | 2020-09-25 | Gilead Sciences Inc | Inhibidores de molecula de muerte programada 1 (pd-1)/ligando de molecula de muerte programada 1 (pd-l1). |
KR102587510B1 (ko) | 2018-02-15 | 2023-10-11 | 길리애드 사이언시즈, 인코포레이티드 | 피리딘 유도체 및 hiv 감염을 치료하기 위한 그의 용도 |
JP7038843B2 (ja) | 2018-02-16 | 2022-03-18 | ギリアード サイエンシーズ, インコーポレイテッド | Retroviridaeウイルス感染の処置において有用な治療用化合物を調製するための方法および中間体 |
CN111788204B (zh) | 2018-02-26 | 2023-05-05 | 吉利德科学公司 | 作为hbv复制抑制剂的取代吡咯嗪化合物 |
TW201945003A (zh) | 2018-03-01 | 2019-12-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 2,4-二胺基喹唑啉衍生物及其醫學用途 |
CN111867582A (zh) | 2018-03-14 | 2020-10-30 | 爱尔兰詹森科学公司 | 衣壳组装调节剂给药方案 |
EP3774883A1 (en) | 2018-04-05 | 2021-02-17 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
KR20200140867A (ko) | 2018-04-06 | 2020-12-16 | 인스티튜트 오브 오가닉 케미스트리 앤드 바이오케미스트리 에이에스 씨알 브이.브이.아이. | 3'3'-사이클릭 다이뉴클레오티드 |
TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | 2,2,─環二核苷酸 |
TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
CA3093130C (en) | 2018-04-19 | 2023-10-17 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
US20190359645A1 (en) | 2018-05-03 | 2019-11-28 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides comprising carbocyclic nucleotide |
EP3817819A1 (en) | 2018-07-03 | 2021-05-12 | Gilead Sciences, Inc. | Antibodies that target hiv gp120 and methods of use |
KR102651420B1 (ko) | 2018-07-06 | 2024-03-28 | 길리애드 사이언시즈, 인코포레이티드 | 치료 헤테로시클릭 화합물 |
US11186579B2 (en) | 2018-07-06 | 2021-11-30 | Gilead Sciences, Inc. | Therapeutic heterocyclic compounds |
AU2019301811B2 (en) | 2018-07-13 | 2022-05-26 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
KR20230141905A (ko) | 2018-07-16 | 2023-10-10 | 길리애드 사이언시즈, 인코포레이티드 | Hiv의 치료를 위한 캡시드 억제제 |
WO2020022272A1 (ja) | 2018-07-23 | 2020-01-30 | 公益財団法人ヒューマンサイエンス振興財団 | インフルエンザワクチンを含む組成物 |
WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
CN112673007A (zh) * | 2018-09-11 | 2021-04-16 | 豪夫迈·罗氏有限公司 | 用于治疗自身免疫性疾病的吡唑并吡啶胺化合物 |
US20200113912A1 (en) | 2018-09-12 | 2020-04-16 | Silverback Therapeutics, Inc. | Methods and Compositions for the Treatment of Disease with Immune Stimulatory Conjugates |
WO2020072656A1 (en) | 2018-10-03 | 2020-04-09 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ, インコーポレイテッド | Pd-1/pd-l1阻害剤 |
CN117105933A (zh) | 2018-10-31 | 2023-11-24 | 吉利德科学公司 | 具有hpk1抑制活性的取代的6-氮杂苯并咪唑化合物 |
KR102650496B1 (ko) | 2018-10-31 | 2024-03-26 | 길리애드 사이언시즈, 인코포레이티드 | Hpk1 억제제로서의 치환된 6-아자벤즈이미다졸 화합물 |
WO2020162705A1 (ko) | 2019-02-08 | 2020-08-13 | 성균관대학교산학협력단 | 톨-유사 수용체 7 또는 8 작용자와 콜레스테롤의 결합체 및 그 용도 |
MA55020A (fr) | 2019-02-22 | 2021-12-29 | Janssen Sciences Ireland Unlimited Co | Dérivés d'amide utiles dans le traitement d'une infection par le virus de l'hépatite b ou de maladies induites par le virus de l'hépatite b |
WO2020176505A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
WO2020176510A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
EP3935066A1 (en) | 2019-03-07 | 2022-01-12 | Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
JP7350871B2 (ja) | 2019-03-07 | 2023-09-26 | インスティチュート オブ オーガニック ケミストリー アンド バイオケミストリー エーエスシーアール,ヴイ.ヴイ.アイ. | 2’3’-環状ジヌクレオチドおよびそのプロドラッグ |
US11766447B2 (en) | 2019-03-07 | 2023-09-26 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
TW202210480A (zh) | 2019-04-17 | 2022-03-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
JP2022532526A (ja) | 2019-05-06 | 2022-07-15 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | Hbv感染又はhbv誘導性疾患の処置において有用なアミド誘導体 |
TW202231277A (zh) | 2019-05-21 | 2022-08-16 | 美商基利科學股份有限公司 | 鑑別對使用gp120 v3聚醣導向之抗體的治療敏感之hiv病患的方法 |
WO2020237025A1 (en) | 2019-05-23 | 2020-11-26 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
WO2020255042A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and a pyrimidine derivative |
WO2020255039A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and quinazoline derivatives |
US20220305115A1 (en) | 2019-06-18 | 2022-09-29 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
WO2020255035A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and pyrimidine derivatives |
MX2021015533A (es) | 2019-06-19 | 2022-02-10 | Silverback Therapeutics Inc | Anticuerpos anti-mesotelina e inmunoconjugados de los mismos. |
BR112021026376A2 (pt) | 2019-06-25 | 2022-05-10 | Gilead Sciences Inc | Proteínas de fusão flt3l-fc e métodos de uso |
TW202115056A (zh) | 2019-06-28 | 2021-04-16 | 美商基利科學股份有限公司 | 類鐸受體調節劑化合物的製備方法 |
CN112174823B (zh) * | 2019-07-01 | 2023-12-01 | 南京富润凯德生物医药有限公司 | 一种合成2,2-二甲基-3-氧杂环丁酮的中间体及其制备方法和应用 |
CA3145791A1 (en) | 2019-07-16 | 2021-01-21 | Gilead Sciences, Inc. | Hiv vaccines and methods of making and using |
US20220257619A1 (en) | 2019-07-18 | 2022-08-18 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
WO2021034804A1 (en) | 2019-08-19 | 2021-02-25 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
BR112022005687A2 (pt) | 2019-09-30 | 2022-06-21 | Gilead Sciences Inc | Vacinas contra o hbv e métodos para tratar o hbv |
WO2021067644A1 (en) | 2019-10-01 | 2021-04-08 | Silverback Therapeutics, Inc. | Combination therapy with immune stimulatory conjugates |
PL4045083T3 (pl) | 2019-10-18 | 2024-05-13 | Forty Seven, Inc. | Terapie skojarzone do leczenia zespołów mielodysplastycznych i ostrej białaczki szpikowej |
MX2022005123A (es) | 2019-10-31 | 2022-05-30 | Forty Seven Inc | Tratamiento basado en anti-cd47 y anti-cd20 para cancer hematologico. |
TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
US11807625B2 (en) | 2019-11-26 | 2023-11-07 | Gilead Sciences, Inc. | Capsid inhibitors for the prevention of HIV |
US20230031465A1 (en) | 2019-12-06 | 2023-02-02 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome |
AU2020412875A1 (en) | 2019-12-24 | 2022-06-23 | Carna Biosciences, Inc. | Diacylglycerol kinase modulating compounds |
AU2021219668A1 (en) | 2020-02-14 | 2022-08-25 | Gilead Sciences, Inc. | Antibodies and fusion proteins that bind to CCR8 and uses thereof |
JP2023514727A (ja) | 2020-02-21 | 2023-04-07 | シルバーバック セラピューティックス インコーポレイテッド | ネクチン-4抗体コンジュゲートおよびその使用 |
WO2021177679A1 (ko) | 2020-03-02 | 2021-09-10 | 성균관대학교산학협력단 | 병원균 외벽 성분 기반 생병원체 모방 나노 입자 및 그 제조 방법 |
KR20220156884A (ko) | 2020-03-20 | 2022-11-28 | 길리애드 사이언시즈, 인코포레이티드 | 4'-c-치환된-2-할로-2'-데옥시아데노신 뉴클레오시드의 프로드러그 및 이의 제조 및 사용 방법 |
MX2022013619A (es) | 2020-05-01 | 2022-11-16 | Gilead Sciences Inc | Compuestos de 2,4-dioxopirimidina que inhiben cd73. |
WO2021236944A1 (en) | 2020-05-21 | 2021-11-25 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising bictegravir |
CA3181690A1 (en) | 2020-06-25 | 2021-12-30 | Chienhung CHOU | Capsid inhibitors for the treatment of hiv |
CA3183993A1 (en) | 2020-07-01 | 2022-01-06 | Peter R. Baum | Anti-asgr1 antibody conjugates and uses thereof |
US20230277525A1 (en) | 2020-08-04 | 2023-09-07 | Progeneer Inc | Conjugate of functional drug and toll-like receptor 7 or 8 agonist of which active site is temporarily inactivated and use thereof |
WO2022031011A1 (ko) | 2020-08-04 | 2022-02-10 | 성균관대학교산학협력단 | 동력학적으로 작용하는 아주번트 앙상블 |
EP4194006A1 (en) | 2020-08-04 | 2023-06-14 | Progeneer Inc. | Mrna vaccine comprising adjuvant capable of kinetic control |
AU2021320236A1 (en) | 2020-08-07 | 2023-04-13 | Gilead Sciences, Inc. | Prodrugs of phosphonamide nucleotide analogues and their pharmaceutical use |
TWI815194B (zh) | 2020-10-22 | 2023-09-11 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
CA3195799A1 (en) | 2020-11-11 | 2022-05-19 | Stephen R. Martin | Methods of identifying hiv patients sensitive to therapy with gp120 cd4 binding site-directed antibodies |
CN117279664A (zh) | 2021-04-10 | 2023-12-22 | 普方生物制药美国公司 | Folr1结合剂、其偶联物及其使用方法 |
TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
EP4326768A1 (en) | 2021-04-23 | 2024-02-28 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
JP2024518558A (ja) | 2021-05-13 | 2024-05-01 | ギリアード サイエンシーズ, インコーポレイテッド | TLR8調節化合物と抗HBV siRNA治療薬との組合せ |
WO2022245671A1 (en) | 2021-05-18 | 2022-11-24 | Gilead Sciences, Inc. | Methods of using flt3l-fc fusion proteins |
EP4359411A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
EP4359389A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
CN117396478A (zh) | 2021-06-23 | 2024-01-12 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
CN117355531A (zh) | 2021-06-23 | 2024-01-05 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
TW202320857A (zh) | 2021-07-06 | 2023-06-01 | 美商普方生物製藥美國公司 | 連接子、藥物連接子及其結合物及其使用方法 |
TW202330504A (zh) | 2021-10-28 | 2023-08-01 | 美商基利科學股份有限公司 | 嗒𠯤—3(2h)—酮衍生物 |
WO2023077030A1 (en) | 2021-10-29 | 2023-05-04 | Gilead Sciences, Inc. | Cd73 compounds |
US20230212148A1 (en) | 2021-12-03 | 2023-07-06 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
CA3235937A1 (en) | 2021-12-03 | 2023-06-08 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
AU2022399845A1 (en) | 2021-12-03 | 2024-05-23 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
US20230220106A1 (en) | 2021-12-08 | 2023-07-13 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
US20230242508A1 (en) | 2021-12-22 | 2023-08-03 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
WO2023122581A2 (en) | 2021-12-22 | 2023-06-29 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
US20230373950A1 (en) | 2022-03-17 | 2023-11-23 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
WO2023183817A1 (en) | 2022-03-24 | 2023-09-28 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
TW202345901A (zh) | 2022-04-05 | 2023-12-01 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
TW202400172A (zh) | 2022-04-06 | 2024-01-01 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
TW202400138A (zh) | 2022-04-21 | 2024-01-01 | 美商基利科學股份有限公司 | Kras g12d調節化合物 |
WO2024006982A1 (en) | 2022-07-01 | 2024-01-04 | Gilead Sciences, Inc. | Therapeutic compounds useful for the prophylactic or therapeutic treatment of an hiv virus infection |
WO2024006929A1 (en) | 2022-07-01 | 2024-01-04 | Gilead Sciences, Inc. | Cd73 compounds |
WO2024015741A1 (en) | 2022-07-12 | 2024-01-18 | Gilead Sciences, Inc. | Hiv immunogenic polypeptides and vaccines and uses thereof |
CN116120282B (zh) * | 2022-08-04 | 2024-02-20 | 苏州系统医学研究所 | 具有ev71和/或cva16病毒抑制活性的化合物及其应用 |
US20240083984A1 (en) | 2022-08-26 | 2024-03-14 | Gilead Sciences, Inc. | Dosing and scheduling regimen for broadly neutralizing antibodies |
US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
WO2024076915A1 (en) | 2022-10-04 | 2024-04-11 | Gilead Sciences, Inc. | 4'-thionucleoside analogues and their pharmaceutical use |
Family Cites Families (90)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2610889B2 (ja) | 1987-09-03 | 1997-05-14 | 日本臓器製薬株式会社 | 新規架橋アデニン誘導体 |
ES2232871T3 (es) | 1996-07-03 | 2005-06-01 | Sumitomo Pharmaceuticals Company, Limited | Nuevos derivados de purina. |
DE69736711T2 (de) | 1996-08-28 | 2007-09-20 | Pfizer Inc. | Substituierte 6,5-heterobicyclische-derivate |
CN1083841C (zh) | 1996-10-04 | 2002-05-01 | 杏林制药株式会社 | 吡唑并吡啶基哒嗪酮衍生物及其制备方法 |
AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
US6339089B2 (en) | 1997-08-13 | 2002-01-15 | Fujirebio Inc. | Pyrimidine nucleus-containing compound and a medicament containing the same for a blood oxygen partial pressure amelioration, and a method for preparing the same |
KR100613634B1 (ko) | 1997-11-28 | 2006-08-18 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 신규한 복소환 화합물 |
TW572758B (en) | 1997-12-22 | 2004-01-21 | Sumitomo Pharma | Type 2 helper T cell-selective immune response inhibitors comprising purine derivatives |
US6187777B1 (en) | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
NZ506417A (en) | 1998-02-17 | 2003-05-30 | Tularik Inc | Anti-viral pyrimidine derivatives |
US6110929A (en) | 1998-07-28 | 2000-08-29 | 3M Innovative Properties Company | Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs thereof |
JP4342007B2 (ja) | 1998-08-10 | 2009-10-14 | 大日本住友製薬株式会社 | キナゾリン誘導体 |
JP4315300B2 (ja) | 1998-08-10 | 2009-08-19 | 大日本住友製薬株式会社 | 新規なキナゾリン誘導体 |
ATE267175T1 (de) | 1998-08-27 | 2004-06-15 | Sumitomo Pharma | Pyrimidin derivate |
US6583148B1 (en) * | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
CA2323008C (en) | 1999-10-11 | 2005-07-12 | Pfizer Inc. | Pharmaceutically active compounds |
WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
WO2003055890A1 (en) | 2001-12-21 | 2003-07-10 | Bayer Pharmaceuticals Corporation | Thienopyrimidine derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
US7091232B2 (en) | 2002-05-21 | 2006-08-15 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
TW200407143A (en) | 2002-05-21 | 2004-05-16 | Bristol Myers Squibb Co | Pyrrolotriazinone compounds and their use to treat diseases |
EP1552842A1 (en) | 2002-06-07 | 2005-07-13 | Kyowa Hakko Kogyo Co., Ltd. | Bicyclic pyrimidine derivatives |
ES2387388T3 (es) | 2002-09-27 | 2012-09-21 | Dainippon Sumitomo Pharma Co., Ltd. | Compuesto de adenina y uso del mismo |
US8455458B2 (en) | 2002-10-16 | 2013-06-04 | Arthrodynamic Technologies, Animal Health Division, Inc. | Composition and method for treating connective tissue damage |
US7410975B2 (en) | 2003-06-20 | 2008-08-12 | Coley Pharmaceutical Group, Inc. | Small molecule toll-like receptor (TLR) antagonists |
GEP20084545B (en) | 2003-09-05 | 2008-11-25 | Anadys Pharmaceuticals Inc | Introducing tlr7 ligands and prodrugs thereof for the treatment of hepatitis c viral infection |
EP1728792A4 (en) | 2004-03-26 | 2010-12-15 | Dainippon Sumitomo Pharma Co | 8-OXOADENINE COMPOUND |
BRPI0509258A8 (pt) | 2004-03-26 | 2019-01-22 | Astrazeneca Ab | composto de 8-oxoadenina 9-substituída |
WO2007084413A2 (en) | 2004-07-14 | 2007-07-26 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
CN101035773B (zh) | 2004-08-10 | 2012-06-06 | 詹森药业有限公司 | 抑制hiv的1,2,4-三嗪-6-酮衍生物 |
MX2007005408A (es) | 2004-11-09 | 2007-05-16 | Hoffmann La Roche | Compuestos de aminoquinazolinas. |
US7498409B2 (en) | 2005-03-24 | 2009-03-03 | Schering Corporation | Screening assay for TLR7, TLR8 and TLR9 agonists and antagonists |
MX2007013780A (es) | 2005-05-04 | 2008-02-05 | Pfizer Ltd | Derivados 2 amido-6-amino-8-oxo purina como moduladores del receptor como tipo peaje (toll) para el tratamiento del cancer y las infecciones virales tal como la hepatitis c. |
AR054122A1 (es) | 2005-05-12 | 2007-06-06 | Tibotec Pharm Ltd | Pirido[2,3-d]pirimidas utiles como inhibidores de hcv, y metodos para la preparacion de las mismas |
US7994360B2 (en) | 2005-05-16 | 2011-08-09 | Xtl Biopharmaceuticals Ltd. | Benzofuran compounds |
TW201402124A (zh) | 2005-08-19 | 2014-01-16 | Array Biopharma Inc | 作為類鐸受體(toll-like receptor)調節劑之8-經取代苯并氮雜呯 |
CN101296907B (zh) | 2005-09-01 | 2013-03-27 | 弗·哈夫曼-拉罗切有限公司 | 作为p2x3和p2x2/3调节剂的二氨基嘧啶类 |
JPWO2007034881A1 (ja) | 2005-09-22 | 2009-03-26 | 大日本住友製薬株式会社 | 新規アデニン化合物 |
US20070099941A1 (en) | 2005-11-02 | 2007-05-03 | Cytovia, Inc. | N-arylalkyl-thienopyrimidin-4-amines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
WO2007063934A1 (ja) | 2005-12-02 | 2007-06-07 | Mitsubishi Tanabe Pharma Corporation | 脂環式複素環化合物 |
AU2007216247A1 (en) | 2006-02-17 | 2007-08-23 | Pfizer Limited | 3 -deazapurine derivatives as TLR7 modulators |
WO2008009078A2 (en) | 2006-07-20 | 2008-01-24 | Gilead Sciences, Inc. | 4,6-dl- and 2,4,6-trisubstituted quinazoline derivatives useful for treating viral infections |
US8673929B2 (en) | 2006-07-20 | 2014-03-18 | Gilead Sciences, Inc. | 4,6-di- and 2,4,6-trisubstituted quinazoline derivatives and pharmaceutical compositions useful for treating viral infections |
BRPI0717907A2 (pt) | 2006-12-07 | 2013-11-05 | Genentech Inc | "composto, composição farmacêutica, métodos para tratar um câncer, para inbir ou modular a atividade da lipídeo quinase, processo para a produçãoo de uma composição farmacêutica, uso de um composto e kit" |
AU2007335962B2 (en) | 2006-12-20 | 2012-09-06 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Antiviral indoles |
PT2510946E (pt) | 2007-02-07 | 2015-11-23 | Univ California | Conjugados de agonistas sintéticos de tlr e suas utilizações |
JP2008222557A (ja) | 2007-03-08 | 2008-09-25 | Kotobuki Seiyaku Kk | ピロロ[3,2−d]ピリミジン誘導体及びこれを有効成分とする医薬組成物 |
US8067413B2 (en) | 2007-03-19 | 2011-11-29 | Astrazeneca Ab | 9-substituted-8-oxo-adenine compounds as toll-like receptor (TLR7 ) modulators |
WO2008114819A1 (ja) | 2007-03-20 | 2008-09-25 | Dainippon Sumitomo Pharma Co., Ltd. | 新規アデニン化合物 |
AR065784A1 (es) | 2007-03-20 | 2009-07-01 | Dainippon Sumitomo Pharma Co | Derivados de 8-oxo adenina,medicamentos que los contienen y usos como agentes terapeuticos para enfermedades alergicas, antivirales o antibacterianas. |
JP5268120B2 (ja) | 2007-05-22 | 2013-08-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンゾイミダゾロンキマーゼ阻害薬 |
PT2170888E (pt) | 2007-06-29 | 2015-08-21 | Gilead Sciences Inc | Purina derivados e sua utilização como moduladores de recetor de tipo toll 7 |
EP2187883A2 (en) | 2007-08-10 | 2010-05-26 | Genelabs Technologies, Inc. | Nitrogen containing bicyclic chemical entities for treating viral infections |
AU2008296545B2 (en) | 2007-08-28 | 2011-09-29 | Irm Llc | 2 -biphenylamino-4 -aminopyrimidine derivatives as kinase inhibitors |
WO2009030998A1 (en) | 2007-09-05 | 2009-03-12 | Coley Pharmaceutical Group, Inc. | Pyrimidine compounds as toll-like receptor (tlr) agonists |
PE20091236A1 (es) * | 2007-11-22 | 2009-09-16 | Astrazeneca Ab | Derivados de pirimidina como immunomoduladores de tlr7 |
DK2238142T3 (da) | 2007-12-24 | 2012-10-08 | Janssen R & D Ireland | Makrocykliske indoler som hepatitis C-virusinhibitorer |
MX2010008697A (es) | 2008-02-07 | 2010-12-07 | Univ California | Tratamiento de enfermedades de la vejiga con un activador de tlr7. |
AU2009241445A1 (en) | 2008-04-28 | 2009-11-05 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
US8946239B2 (en) | 2008-07-10 | 2015-02-03 | Duquesne University Of The Holy Spirit | Substituted pyrrolo, -furano, and cyclopentylpyrimidines having antimitotic and/or antitumor activity and methods of use thereof |
UY31982A (es) | 2008-07-16 | 2010-02-26 | Boehringer Ingelheim Int | Derivados de 1,2-dihidropiridin-3-carboxamidas n-sustituidas |
DK2313111T3 (da) | 2008-08-01 | 2013-12-02 | Ventirx Pharmaceuticals Inc | Toll-lignende receptoragonistformuleringer og anvendelse deraf |
EA201101650A1 (ru) | 2009-05-21 | 2012-07-30 | Астразенека Аб | Новые производные пиримидина и их применение в лечении злокачественных новообразований и последующих заболеваний |
US8637525B2 (en) | 2009-07-31 | 2014-01-28 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
TWI468402B (zh) | 2009-07-31 | 2015-01-11 | 必治妥美雅史谷比公司 | 降低β-類澱粉生成之化合物 |
EP2491033A4 (en) | 2009-10-20 | 2013-03-13 | Eiger Biopharmaceuticals Inc | AZAINDAZOLES FOR THE TREATMENT OF FLAVIVIRIDAE VIRUS INFECTION |
WO2011049825A1 (en) | 2009-10-22 | 2011-04-28 | Gilead Sciences, Inc. | Derivatives of purine or deazapurine useful for the treatment of (inter alia) viral infections |
KR101094446B1 (ko) | 2009-11-19 | 2011-12-15 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 가지는 2,4,7-치환된 티에노[3,2-d]피리미딘 화합물 |
JP2013032290A (ja) | 2009-11-20 | 2013-02-14 | Dainippon Sumitomo Pharma Co Ltd | 新規縮合ピリミジン誘導体 |
DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
CA2812787A1 (en) | 2010-10-01 | 2012-04-05 | Robert Hershberg | Methods for the treatment of allergic diseases |
WO2012066335A1 (en) | 2010-11-19 | 2012-05-24 | Astrazeneca Ab | Phenol compounds als toll -like receptor 7 agonists |
WO2012067269A1 (en) | 2010-11-19 | 2012-05-24 | Dainippon Sumitomo Pharma Co., Ltd. | Aminoalkoxyphenyl compounds and their use in the treatment of disease |
ME03782B (me) | 2011-04-08 | 2021-04-20 | Janssen Sciences Ireland Unlimited Co | Derivati pirimidina za tretman virusnih infekcija |
JP6050329B2 (ja) | 2011-05-18 | 2016-12-21 | ヤンセン・サイエンシズ・アイルランド・ユーシー | ウイルス感染およびその他の疾患を治療するためのキナゾリン誘導体 |
LT2776439T (lt) | 2011-11-09 | 2018-10-10 | Janssen Sciences Ireland Uc | Purino dariniai, skirti virusinų infekcijų gydymui |
MY169159A (en) | 2012-02-08 | 2019-02-19 | Janssen R&D Ireland | Piperidino-pyrimidine derivatives for the treatment of viral infections |
CN106977495B (zh) | 2012-04-24 | 2020-08-04 | 沃泰克斯药物股份有限公司 | Dna-pk抑制剂 |
WO2014009509A1 (en) | 2012-07-13 | 2014-01-16 | Janssen R&D Ireland | Macrocyclic purines for the treatment of viral infections |
US9284304B2 (en) | 2012-08-10 | 2016-03-15 | Janssen Sciences Ireland Uc | Substituted pyrimidines as toll-like receptor modulators |
EP2712866A1 (en) | 2012-10-01 | 2014-04-02 | Centre National de la Recherche Scientifique (CNRS) | 1,2,4-triazine derivatives for the treatment of viral infections |
ES2701098T7 (es) | 2012-10-05 | 2021-02-03 | Janssen Sciences Ireland Unlimited Co | Derivados de acilaminopirimidina para el tratamiento de infecciones víricas y otras enfermedades |
ES2670513T3 (es) | 2012-10-10 | 2018-05-30 | Janssen Sciences Ireland Uc | Derivados pirrolo[3,2-d]pirimidínicos para el tratamiento de infecciones víricas y otras enfermedades |
MX361585B (es) | 2012-11-16 | 2018-12-11 | Janssen Sciences Ireland Uc | Derivados 2-aminoquinazolínicos sustituidos heterocíclicos para el tratamiento de infecciones víricas. |
UA118751C2 (uk) | 2013-02-21 | 2019-03-11 | ЯНССЕН САЙЄНСІЗ АЙРЛЕНД ЮСі | Похідні 2-амінопіримідину для лікування вірусних інфекцій |
EA202090547A3 (ru) | 2013-03-29 | 2020-12-30 | Янссен Сайенсиз Айрлэнд Юси | Макроциклические деаза-оксипурины для лечения вирусных инфекций |
EP3004074B1 (en) | 2013-05-24 | 2017-10-25 | Janssen Sciences Ireland UC | Pyridone derivatives for the treatment of viral infections and further diseases |
DK3030563T3 (da) | 2013-06-27 | 2017-11-20 | Janssen Sciences Ireland Uc | Pyrrolo-[3,2-d]-pyrimidin-derivater til behandling af virale infektioner og andre sygdomme |
MX368625B (es) | 2013-07-30 | 2019-10-08 | Janssen Sciences Ireland Uc | Derivados de tieno[3,2-d]pirimidinas para el tratamiento de infecciones virales. |
US9701661B2 (en) | 2014-07-11 | 2017-07-11 | Northwestern University | 2-imidazolyl-pyrimidine scaffolds as potent and selective inhibitors of neuronal nitric oxide synthase |
US11053256B2 (en) | 2016-07-01 | 2021-07-06 | Janssen Sciences Ireland Unlimited Company | Dihydropyranopyrimidines for the treatment of viral infections |
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